Isoflurane (Liquid) Instructions for Use

Marketing Authorization Holder

Piramal Enterprises, Limited (India)

ATC Code

N01AB06 (Isoflurane)

Active Substance

Isoflurane (Rec.INN registered by WHO)

Dosage Form

Isoflurane

Inhalation solution: 100 or 250 ml bottle

Dosage Form, Packaging, and Composition

Inhalation solution clear, colorless, volatile, with a characteristic odor.

100 ml – bottles – cardboard packs for healthcare institutions.
250 ml – bottles – cardboard packs for healthcare institutions.

Clinical-Pharmacological Group

Inhalation anesthesia preparation

Pharmacotherapeutic Group

Inhalation anesthetic agent

Pharmacological Action

A halogen-containing agent for inhalation anesthesia. It causes rapid onset of general anesthesia, weakening of pharyngeal and laryngeal reflexes, and moderate muscle relaxation.

With increasing depth of general anesthesia, blood pressure decreases proportionally, heart rate does not change, and spontaneous breathing weakens. The decrease in blood pressure occurs during the induction stage but normalizes during the surgical phase; further deepening of anesthesia leads to significant arterial hypotension.

During mechanical ventilation with normal pCO₂, cardiac output remains constant, regardless of the depth of general anesthesia, and is maintained mainly by an increase in heart rate.

With spontaneous ventilation leading to hypercapnia, which increases heart rate, cardiac output may exceed the initial level.

During light anesthesia, cerebral blood flow does not change but tends to increase during deep anesthesia, which can lead to a transient increase in cerebrospinal fluid (CSF) pressure. The increase in CSF pressure can be prevented or reduced by hyperventilation before or during anesthesia.

The slight irritant effect of isoflurane may limit the induction rate.

Changes in EEG and seizure activity are extremely rare with the use of isoflurane.

Isoflurane increases myocardial sensitivity to the action of adrenaline significantly less than enflurane.

At a normal level of general anesthesia, muscle relaxation may be adequate for some surgical procedures, but significantly smaller doses of muscle relaxants are required to enhance it.

Pharmacokinetics

Only a small part of isoflurane is metabolized in the body. In the postoperative period, only 0.17% of isoflurane can be detected as metabolites in the urine. The C_max of inorganic fluoride in blood serum is on average significantly less than the level of 5 mmol/l and is detected within 4 hours after anesthesia, returning to normal within the next 24 hours.

Indications

For inhalation anesthesia in combination with oxygen or with an oxygen + nitrous oxide mixture.

ICD codes

Dosage Regimen

Determine the dosage individually based on the patient’s age, clinical status, and the requirements of the surgical procedure.

Administer isoflurane only using a vaporizer calibrated specifically for isoflurane to ensure accurate delivery of the intended concentration.

For induction of anesthesia in adults, use an inspired concentration of 1.5% to 3.0% isoflurane with oxygen or a mixture of oxygen and nitrous oxide.

For maintenance of anesthesia, adjust the concentration to 1.0% to 2.5% isoflurane, which is typically sufficient when combined with nitrous oxide.

When used with oxygen alone, higher maintenance concentrations of isoflurane, up to 2.5% to 3.5%, may be required.

For geriatric patients, use lower concentrations of isoflurane to maintain the surgical plane of anesthesia, as they require less anesthetic agent.

In patients also receiving opioid or benzodiazepine premedication, reduce the required concentration of isoflurane accordingly.

Continuously monitor blood pressure and respiratory parameters, as the depth of anesthesia can change rapidly; arterial hypotension and respiratory depression are key indicators of anesthetic depth.

Be aware that isoflurane potentiates the effects of non-depolarizing muscle relaxants; significantly reduce the dosage of these agents.

For pediatric induction, concentrations of up to 3.0% may be used; however, exercise caution in newborns and children under 2 years of age.

Adverse Reactions

From the hematopoietic system: frequency unknown – carboxyhemoglobinemia.

From the immune system: frequency unknown – hypersensitivity reactions, anaphylactic reaction.

From metabolism: frequency unknown – hyperkalemia, increased blood glucose concentration.

From the psyche: frequency unknown – agitation, delirium, mood changes.

From the nervous system: frequency unknown – convulsions, mental disorder.

From the cardiovascular system: frequency unknown – arrhythmia, bradycardia, tachycardia, arterial hypotension, cardiac arrest, QT interval prolongation on ECG, polymorphic ventricular tachycardia of the “torsades de pointes” type, bleeding.

From the respiratory system: frequency unknown – bronchospasm, dyspnea, wheezing, respiratory depression, laryngospasm.

From the digestive system: frequency unknown – intestinal obstruction, nausea, vomiting.

From the liver and biliary tract: frequency unknown – liver necrosis, hepatocellular damage, increased blood bilirubin concentration.

From the skin and subcutaneous tissues: frequency unknown – facial edema, contact dermatitis, rash.

From the urinary system: frequency unknown – decreased blood urea nitrogen concentration, increased blood creatinine concentration.

From the musculoskeletal system: frequency unknown – myoglobinuria, rhabdomyolysis.

General reactions: frequency unknown – malignant hyperthermia, chest discomfort, chills.

From laboratory parameters: frequency unknown – transient leukocytosis, increased activity of liver enzymes, increased fluoride concentration, abnormal changes on EEG, decreased plasma cholesterol concentration, decreased blood alkaline phosphatase activity, increased blood creatine phosphokinase activity.

Contraindications

Hypersensitivity to isoflurane; history of malignant hyperthermia. When used in dentistry, Isoflurane is contraindicated in non-hospitalized patients or patients undergoing surgery on an outpatient basis outside a day hospital (children and adults).

With caution in newborns and children under 2 years of age; in patients with diabetes mellitus; hypovolemia, arterial hypotension and other hemodynamic disorders; liver diseases, or those receiving treatment with drugs known to have side effects on liver function; myasthenia gravis; tendency to develop bronchoconstriction; coronary artery disease; predisposition to develop “corary steal” syndrome; increased intracranial pressure (ICP) or risk of its development.

Use in Pregnancy and Lactation

During pregnancy and breastfeeding, it should be used only after consultation with a doctor, in cases where the intended benefit to the mother outweighs the potential risk to the fetus or infant.

If it is necessary to use isoflurane during lactation, breastfeeding should be discontinued for 12 hours after the use of isoflurane.

Use in Hepatic Impairment

It should be used with caution in patients with impaired liver function.

Pediatric Use

It should be used with caution in newborns and children under 2 years of age.

Geriatric Use

To maintain the surgical stage of anesthesia in elderly patients, lower concentrations of isoflurane are usually required.

Special Precautions

Like other potent general anesthetics, Isoflurane should be used only in the presence of appropriate anesthesiological equipment by qualified specialists who are well familiar with the pharmacology of isoflurane, have undergone training and have experience in managing patients under anesthesia.

When administering isoflurane, the level of general anesthesia can change quickly and easily, so it is recommended to use only carefully calibrated vaporizers or to conduct monitoring that allows assessment of the inhaled concentration. The degree of arterial hypotension and respiratory depression may be indicators of the depth of general anesthesia. With increasing depth of general anesthesia, spontaneous breathing is depressed.

When using isoflurane, constant monitoring of blood pressure levels and external respiration parameters is recommended.

Supportive measures may be required to correct arterial hypotension and respiratory depression due to deepening of the level of general anesthesia.

Effect on ability to drive vehicles and operate machinery

Isoflurane may affect the ability to drive vehicles and operate machinery. The patient should not drive vehicles or operate machinery for at least 24 hours after isoflurane anesthesia. Changes in behavior and intellectual function may persist for up to 6 days after the use of isoflurane. This should be taken into account when the patient resumes normal daily activities, including driving vehicles or operating dangerous machinery.

Drug Interactions

Isoflurane significantly potentiates the action of non-depolarizing muscle relaxants.

Neostigmine eliminates the effect of muscle relaxants but does not affect the muscle relaxation caused by isoflurane itself.

Contraindicated combinations. Non-selective MAO inhibitors: risk of hypertensive crisis during surgery. Treatment should be discontinued 15 days before surgery. Concomitant use of inhalation anesthetics and MAO inhibitors may increase the risk of hemodynamic instability during surgery and other medical procedures.

Not recommended combinations. Beta-adrenomimetics (isoprenaline), as well as alpha- and beta-adrenomimetics (epinephrine or adrenaline; norepinephrine or noradrenaline): risk of serious ventricular arrhythmia due to increased heart rate.

Combinations requiring caution.

Beta-blockers: risk of blockade of cardiovascular compensation mechanisms, resulting in enhanced negative inotropic effects and arterial hypotension. During surgery, the effect of beta-blockers can be suppressed by using beta-adrenomimetics. As a rule, there is no need to discontinue beta-blocker treatment, and a sudden dose reduction should also be avoided.

Isoniazid: the risk of hepatotoxic effects increases, which is associated with increased synthesis of a toxic metabolite of isoniazid. Isoniazid treatment should be interrupted one week before surgery and not resumed for at least 15 days after it.

Epinephrine (adrenaline) when administered subcutaneously or into the gum to achieve local hemostasis: the risk of severe ventricular arrhythmia increases due to increased heart rate.

Indirect sympathomimetics (amphetamines and their derivatives, psychostimulants, appetite suppressants, ephedrine and its derivatives): risk of episodes of increased blood pressure during surgery. It is preferable to discontinue these drugs several days before surgery.

In most cases, if the use of these drugs is absolutely necessary, they should not be discontinued before general anesthesia, but it is important to inform the anesthesiologist about their intake.

Muscle relaxants: risk of enhanced action of depolarizing and, especially, non-depolarizing muscle relaxants.

As a rule, in anesthetic concentrations, Isoflurane at equilibrium reduces the ED95 of succinylcholine, atracurium, pancuronium, rocuronium, and vecuronium by approximately 25-40% or more compared with anesthesia with N₂O and opioid agents.

Narcotic analgesics: potentiate the depressant effect of isoflurane on the respiratory system.

Opioids: reduce the MAC of isoflurane. When isoflurane and opioid agents, such as fentanyl and its analogues, are used together, a synergistic effect may manifest as a drop in blood pressure and a decrease in respiratory rate. In patients receiving opioids, benzodiazepines, or other sedative drugs, minimal doses of isoflurane should be used.

Slow calcium channel blockers: Isoflurane may lead to pronounced arterial hypotension when used in patients being treated with slow calcium channel blockers, especially dihydropyridine derivatives.

In patients who have taken St. John’s wort preparations for a long time, pronounced arterial hypotension and delayed recovery from anesthesia with halogenated inhalation anesthetics have been observed.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.